Several different alkoxycarbonyl-substituted 2-benzoxazolinone moieties have been incorporated into a tetrahydroisoindoline-1,3-dione scaffold to provide 25 compounds (1a–1u and 2a–2d). The structures of these compounds were confirmed by ¹H and ¹³C NMR, HRMS and X-ray single-crystal diffraction. Some of these compounds (1g, 1h, 1j, 1k) exhibited excellent herbicidal activities against Abutilon theophrasti, Amaranthus retroflexus and Echinochloa crus-galli at a rate of 375 g AI·ha⁻¹. Among them, compounds 1h and 1j displayed the best post-emergence herbicidal effect against Abutilon theophrasti with ED₅₀ values of 1.8 and 5.3 g AI·ha⁻¹, respectively, which are superior to that of the commercial acifluorfen (44.3 g AI·ha⁻¹). Field trials demonstrated that compound 1h exhibited similar herbicidal activity to a high concentration atrazine, and found to be safer for maize than atrazine. The results of this study therefore show that compound 1h could potentially be used as a post-emergence herbicide for maize fields.

Gossypol dient der Abwehr von Schädlingen und Pathogenen in Baumwollpflanzen. Seine Biosynthese umfasst die oxidative Kupplung von Hemigossypol, die zu zwei Atropisomeren führt. In vivo dominiert (+)-Gossypol, was auf eine stereochemisch kontrollierte Biosynthese schließen lässt. Ziel dieser Studie waren die Identifizierung der Faktoren für die Bildung von (+)-Gossypol sowie die Untersuchung ihres Potenzials für die Synthese asymmetrischer Biaryle. Die Kupplung von Hemigossypol mit Laccase und O₂ als Oxidationsmittel in Gegenwart eines dirigierenden Proteins (DIR) von Gossypium hirsutum (GhDIR4) verläuft atropselektiv. (+)-Gossypol wurde mit >80 % ee erhalten, während in Abwesenheit von GhDIR4 nur racemisches Gossypol entstand. Die Identifizierung von GhDIR4 unterstreicht die Bedeutung von DIRs im Sekundärstoffwechsel von Pflanzen und könnte ein erster Schritt zur Entwicklung von DIRs für die Synthese axial-chiraler Binaphthyle sein.

Gossypol is a defense compound in cotton plants for protection against pests and pathogens. Gossypol biosynthesis involves the oxidative coupling of hemigossypol and results in two atropisomers owing to hindered rotation around the central binaphthyl bond. (+)-Gossypol predominates in vivo, thus suggesting stereochemically controlled biosynthesis. The aim was to identify the factors mediating (+)-gossypol formation in cotton and to investigate their potential for asymmetric biaryl synthesis. A dirigent protein from Gossypium hirsutum (GhDIR4) was found to confer atropselectivity to the coupling of hemigossypol in presence of laccase and O₂ as an oxidizing agent. (+)-Gossypol was obtained in greater than 80 % enantiomeric excess compared to racemic gossypol in the absence of GhDIR4. The identification of GhDIR4 highlights a broader role for DIRs in plant secondary metabolism and may eventually lead to the development of DIRs as tools for the synthesis of axially chiral binaphthyls.

A concise method for the synthesis of 1,2-fused tricyclic indole scaffolds by domino cyclization involving a Pd-catalyzed Sonogashira coupling, indole cyclization, regio- and chemoselective N-1 acylation, and 1,4-Michael addition is reported. This method provides straightforward access to tetrahydro[1,4]diazepino[1,2-a]indole and hexahydro[1,5]diazocino[1,2-a]indole scaffolds.

A series of 7-methoxycryptopleurine derivatives 2–23 were prepared and evaluated for their antiviral activity against tobacco mosaic virus (TMV) for the first time. The bioassay results showed that most of these compounds exhibited excellent in vivo anti-TMV activity, of which 7-methoxycryptopleurine salt derivatives 16, 19, and 23 displayed significantly higher activity than 7-methoxycryptopleurine (1) and commercial ribavirin and ningnanmycin. Salification, the most commonly employed method for modifying physical-chemical properties, did significantly increase antiviral activity, and different salt forms displayed different antiviral effect. This study provides fundamental support for development and optimization of phenanthroquinolizidine alkaloids as potential inhibitors of plant virus.

With the aim of optimizing the structure of tenuazonic acid and improving the herbicidal activity, hydrazine moieties were introduced to the 3-position of pyrrolidine-2,4-dione scaffold of tenuazonic acid. 3-Hydrazido-pyrrolidine-2,4-dione compounds (4a, 4b, 4c, 4d, 4e) were prepared from corresponding carboxylates and hydrazines via a microwave-assisted amidation, whereas 3-hydrazono compounds (7a, 7b, 7c, 7d, 7e) were prepared from corresponding 3-acetyl pyrrolidine-2,4-dione. Both of the two structures also exhibited herbicidal activities, especially against the dicotyledonous species amaranth pigweed (Amaranthus retroflexus), but with different structure-activity relationship.

In order to study the potential bioactivities of 4-amino tetramic acid derivatives, the 4-amination products of pyrrolidine-2,4-diones (5) and 4-hydroxy-2-oxo-2,5-dihydro-1H-pyrrole-3-carboxylates (4) were prepared. The 4-amination of 5 took place in high yield when catalyzed by acetic acid, whereas the 4-amination of 4 was achieved through a 4-ethoxy intermediate, which was prepared by acidic etherification. Their herbicidal, fungicidal, insecticidal, and antitumor activities were tested. The bioassays showed that two of the compounds exhibited good herbicidal activity against dicot Arabidopsis thaliana at a concentration of 10 µg/mL, and one compound gave instinct fungicidal activity against Pythium sp. at a concentration of 2 µg/mL.

The first enantioselective approach to 13a-methyl-14-hydroxyphenanthroindolizidine alkaloids was achieved in six linear steps from phenanthryl alcohol and features a highly substrate-dependent Parham cycloacylation and Seebach's enantioselective alkylation as the key steps. The route is concise, protecting-group free, provides access to all stereoisomers, and works on a gram scale. In addition to the putative structure of hypoestestatin 2, the other three stereoisomers and two structurally related analogues were synthesized, none of which shows identical NMR spectra to those reported for natural hypoestestatin 2, which indicates that further structure revision is required.

A practical and scalable route was developed for the total synthesis of gossypol to allow for the construction of dozens of gossypol derivatives. tBuO₂Ac was found to be a highly efficient oxidant for the polymerization of hemigossypol through a biosynthetic process under nonenzymatic conditions to give gossypol. Hemigossypol was synthesized on a gram scale by starting from commercially available carvacrol and dimethyl succinate and using a Stobbe condensation, an electrophilic cyclization, and the Michael addition of ortho-quinone methide as key steps.

A concise, efficient and modular route involving Parham-type cycloacylation as the key step has been used to synthesize six enantiopure phenanthro-indolizidine alkaloids 1a–c. The preparation of enantiomerically pure tylophora alkaloids and their seco analogues on a large-scale is now feasible. The alcohol intermediates 8a–c, which are difficult to prepare by other synthetic methodologies, have been synthesized by a metallation–cyclization–reduction sequence in excellent yields.

The first synthesis of (±)-boehmeriasin A and B and a concise synthesis of (±)-cryptopleurine and (±)-hydroxycryptopleurine are described. The piperidine ring of these alkaloids was constructed by the coupling of the phenanthrene ring with 2-bromopyridine through a nucleophilic substitution reaction and subsequent reduction of the resulting pyridyl ketone. The first crystal structure of a phenanthro-quinolizidine alkaloid is also reported. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Iron(III) chloride has been used to prepare the polymethoxy substituted phenanthrene derivatives via intramolecular oxidative coupling of (E or Z)-2,3-di(substituted phenyl)acrylate at room temperature in excellent yields. Mild reaction conditions and the use of inexpensive and nontoxic FeCl₃ provide a novel practical and large-scaled viable route for the synthesis of the important phenanthrene rings.